Coumarin anticoagulants, such as dicumarol or warfarin, are involved in interactions with drugs from various classes. This often creates a problem in medicine in that a therapeutic regimen is altered from that which is desired. The number of reports of such interactions is so vast that a computer based retrieval system was developed at this Medical Center for the retrieval of information concerning drug interactions involving the coumarin anticoagulants and other drugs. Recent studies have shown that dicumarol and warfarin are excreted in the bile of rat rather than in the urine. Furthermore, the excretion of dicumarol was found to be accelerated by induction with phenobarbital and inhibited by SKF 525-A. The excretion of warfarin was accelerated by tolbutamide and reduced by novobiocin. The effects of other drugs on the excretion of coumarin anticoagulants in the bile of rats will be studied. Labeled anticoagulant will be injected into anesthetized rats and the bile will be collected for radioactivity determinations. Studies indicate the radioactivity in the bile is in the form of metabolites. Experiments will be carried out to identify the warfarin metabolites. Possible sites of drug interactions which will be investigated are (1) competition for binding sites on serum albumin utilizing equilibrium dialysis, (2) sites of drug metabolism and (3) sites of biliary excretion of drugs. Among the drug classes or agents which will be studied are antibiotics, sedatives, anti-inflammatory agents, environmental agents, enzyme inducers and hepatotoxins. The objectives are to identify and analyze the factors which influence the excretion of the anticoagulants in the bile so that these drugs may be used safely and effectively.